Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation

作者：Wenqi Li, Shuwen Zhu, Jing Liu, Zhigang Liu, Miao Yang, Jianwei Zhang, Shimeng Li, Qianyi Zhang, Zhichao Liu, Yue Yang, Li Chen, Xiaowei Guo, Tiantian Zhang, Lingxin Meng, Dan Chai, Guodong Tang, Xiaohe Li, Honggang Zhou, Cheng Yang · 发表于：Preprints.org · 年份：2023 · DOI：10.20944/preprints202306.1297.v1 · 被引用次数：5 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Peptidase Inhibition and Analysis、HER2/EGFR in Cancer Research

(1) Background: Heart failure (HF) is the final stage of multiple cardiac diseases, which has now become a severe public health problem worldwide. β-Adrenergic receptor (β-AR) overactivation is a major pathological factor associated with multiple cardiac diseases and mediates cardiac fibrosis and inflammation. Previous study has demonstrated that Bruton's tyrosine kinase (BTK) mediated cardiac fibrosis by TGF-β related signal pathways, indicating that BTK was a potential drug target for cardiac fibrosis. Zanubrutinib, a second-generation BTK inhibitor, has shown anti-fibrosis effects in previous research. However, it is unclear whether Zanubrutinib can alleviate cardiac fibrosis induced by β-AR overactivation;(2) Methods: In vivo: Male C57BL/6J mice were treated with or without the β-AR agonist isoproterenol (ISO) to establish cardiac fibrosis animal model. Here, results showed that BTK inhibitor Zanubrutinib (ZB) had a great effect on cardiac fibrosis and inflammation induced by β-AR. In vitro: Results showed that ZB alleviated β-AR-induced cardiac fibroblast activation and macrophage proinflammatory cytokine production. Further mechanism studies demonstrated that ZB inhibited β-AR-induced cardiac fibrosis and inflammation by BTK、STAT3、NF-κB and PI3K/Akt signal pathways both in vivo and in vitro; (4) Conclusions: our research provides evidence that ZB ameliorates β-AR-induced cardiac fibrosis and inflammation.